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Radioiodine is a therapy that is used to treat disorders of the thyroid gland. Most notably it is used to treat hyperthyroidism/thyrotoxicosis and thyroid cancer (follicular and papillary) It has been used as therapy for thyrotoxicosis for over 50 years in adults The treatment is delivered as an oral capsule or solution, containing the active isotope I131 –which has an 8 day half life. As the thyroid glands normal function is to take up iodine the I131 is accumulated in the gland. Radioactive decay leads to emission of B particles which cause direct damage to surrounding follicles or cause indirect damage to other cells. This leads to accumulation of mutations that are often lethal to the cells causing destruction of the thyroid tissue. The radioisotopes have a particular affinity for the cells in the thyroid that are overactive and therefore dividing at a faster rate this results in partial destruction or complete ablation of the thyroid depending on dose administered.

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The topic of the safety of radioiodine is of important as there is often concern about exposing children to radiation exposure – several high profile incidents e.g. Chernobyl have highlighted the dangers of external exposure to radiation This has led to divided approaches in the treatment of hyperthyroidism in the USA uptake of radioiodine is more routine whereas in the UK historically it has been less common for patients to be offered RAI unless first line treatment with antithyroid medications has failed. Radioiodine therapy is used far more commonly in the adult population with hyperthyroidism In children concerns are centred around the growing child in whom cells are more rapidly dividing and therefore perceived to be at increased risk of developing mutations with a longer life span in which cancerous mutations can occur. There is also concern about damage to the germ cells and risk to the child’s future offspring. It is therefore important to review the evidence to clarify whether there is any evidence that therapeutic radioiodine poses risks or dangers to the paediatric population

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Hyperthyroidism is by definition an ‘overactive’ thyroid gland. It is a condition associated with high levels circulating thyroid hormones Graves’ disease is the main cause in of this in children. It is an autoimmune process in which the body develops antibodies to TSH receptors of the cells in the thyroid gland. These autoantibodies attach to the TSH receptor mimicking TSH and causing receptor activation. This leads to the release of thyroxine (T4) and triiodothyronine (T3) Common features: Eye problems include proptosis/exopthalmos with wide palpebral fissures and stare. Lid lag and optic atrophy often feature. Goitre: non-tender symmetrical enlargement of the thyroid gland Symptoms often lead to behavioural problems and social disturbance and some children present with similar features to ADHD Few children undergo spontaneous remission – so treatment is required to manage their symptoms

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There are a number of methods of managing hyperthyroidism – B blockers: can be used to provide relief from symptoms e.g. propranolol Antithyroid medications e.g. carbimazole. These cause side effects in 20-30% of children including leukopenia (reduced WBC), hepatitis, skin reactions and aplastic anaemia. Their action is mediated by conversion of carbimazole to methimazole which acts on thyroid peroxidase to reduce free hormone production Surgical resection : This is associated with the risk of vocal cord paralysis due to damage to the recurrent laryngeal nerve and also hypocalcaemia. Unless completely resected there is an ongoing risk of recurrence. Radioiodine I will explore the safety of radioiodine in the rest of this presentation

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Cardis et. al. 2005 explored the effects of external exposure to radiation following the Chernobyl disaster. This environmental radiation was composed largely of radioactive isotopes of iodine. The Increased risk of thyroid cancer was determined to be mostly due to the I 131 isotope. The risk of developing thyroid cancer was three times higher in iodine deficient areas Risk could be reduced by 3 times by providing iodine supplementation Linear dose response relationship up to 2Gray Kazakov 1992 outline that the thyroid cancers developing amongst this population were primarily papillary carcinomas

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Effects of the Chernobyl radiation disaster: This led to a large increase in the incidence of thyroid cancer in children and adolescents as outlined above. The effects began to be seen less than 5 years after the incident Increased from less than 1 / 100, 000 children to 8/100,000 in 2002. There is a thought that children are more susceptible to the effects of radiation due to their smaller thyroid glands and the higher rate of cell division as they grow which increases the opportunity for malignant mutation of cells. However the authors of the above study also identified that much of the population was iodine deficient at the time of the incident and that this can lead to increased uptake of radioactive iodine causing the thyroid gland to be flooded with radioactive iodine from the environment

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Short term side effects: Clark et. al. 1995 – looked at short term effects of RAI in children & found that vomiting, thyroiditis and thyroid nodules were the most common outcomes 90% of those children treated for whom the treatment aim was to ablate the thyroid become hypothyroid and required lifelong medication with thyroxine to restore thyroid hormones. This can be problematic if compliance is poor. The adolescent outlined in the earlier case study gained 20kg in the first year following RAI. Thyroid storm: This is linked to excess thyroid hormone release in the 15 days following treatment and can lead to tachycardia, jaundice, dehydration, agitation and confusion. There are rare reports of this in the literature and there is some debate as to whether the true cause is related to withdrawal of antithyroid medications before providing RAI. Hypothyroidism – need to take lifelong thyroxine replacement therapy – can be a problem if the child stuggles with compliance!

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Thyroid cancer- Rivkees – point out that higher doses of radioiodine are used in therapeutic treatment – iodine deficiency played a part in the after effects of the Chernobyl disaster. External radiation often contains multiple isotopes of radioactive iodine and it is not possible to attribute the total effect to I131 alone. Robbins and Schneider suggest that the higher dose of radioiodine associated with RAI therapy is more likely to induce cell death leading to less potential for oncogenic mutations to develop Saenger – focussed on the association between radioiodine and leukemia. They found that the risk was the same for those undergoing radioiodine vs. surgical approach Other studies have looked at whether the risk of other cancers are increased however no significant increases have been detected Risk to offspring: Both Read and Freitas suggest that there is no increase in risk of miscarriage or congenital abnormality following treatment with radioiodine. A study looking at pregnant women found that exposure in utero is linked with hypothyroidism in the child and the development of figurative memory impairment Ophthalmology: Ophthalmological complications of hyperthyroidism have been observed to be worsened in adults who had RAI – but the same effect has not been

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seen in children. Where it does occur can be treated with steroids.

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http://news.bbc.co.uk/1/hi/health/4216102.stm http://www.bbc.co.uk/news/science-environment-12789749

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